Abstract
Of primary concern to an investigator of neurological disorders is that of the selection of the most relevant animal model to achieve his or her research goals. According to Kornetsky (1977), three different types of animal models are typically used in medical research. Homologous models are those in animals which the etiology, symptoms, and outcome of the model duplicate those of the human disorder in every major aspect. Isomorphic models are those that resemble the human disorder, but are artificially produced in the laboratory in a way that does not reflect normal human etiology, and predictive models are those that do not necessarily resemble the human disorder in many respects, but are valuable in terms of predicting some aspect of the disorder such as the response to various drugs. The selection of the model depends on the goal of the experimenter. A predictive model allows the investigator to make certain predictions about the disorder it models; an isomorphic model permits not only predictions, but also allows the study of underlying mechanisms; and a homologous model serves as a basis for studying all aspects of a disorder, including its causes. Once the purpose of the experiment is defined, the type of model to be selected becomes apparent.
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References
Abel, M S and McCandless, D. W (1992) The kindling model of epilepsy, in Neuromethods vol 22 Animal Models of Neurological Disease, II, (Boulton, A A, Baker, G B, and Butterworth, R F, eds), Humana, Clifton, NJ, pp 153–168
Antal, A. and Bodis-Wollner, I (1993) Animal models of Alzheimer’s, Parkinson’s and Huntington’s disease A minireview Neurobiology 1, 101–122.
Beal, M. F, Kowall, N W, Ellison, D W, Mazurek, M F, Swartz, K J, and Martin, J B (1986) Replication of the neurochemical characteristics of Huntington’s disease by qumolinic acid Nature 321, 168–171
Beal, M F, Kowall, N. W, Swartz, K. J, Ferranti, R J, and Martin, J. B (1988) Systemic approaches to modifying lesions in rats J Neurosa 8, 3901–3908
Bedard, P J, Boucher, R, Gomez-Mancilla, B, and Blanchette, P. (1992) Primate models of Parkinson’s disease, in Neuromethods, vol 21 Animal Models of Neurological Disease, I, (Boulton, A A., Baker, G B., and Butterworth, R F., eds.), Humana, Clifton, NJ, pp 159–173.
Borlongan, C V., Cahill, D W, and Sanberg, P R. (1995) Locomotor and passive avoidance deficits followign occlusion of the middle cerbral artery Physiol Behav 58, 909–917
Buonnamici, M, Maj, R., Pagani, F, Rossi, A. C, and Khazan, N (1986) Tremor at rest episodes in unilaterally 6-OHDA-induced substantia nigra lesioned rats. EEG-EMG and behavior Neuropharmacology 25, 323–325
Burns, R S, Chiueh, C. C, Marky S P., Ebert M H, Jacobowitz, D M., and Kopin, I J (1983) A primate model of parkinsonism selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by l-methyl-4-phenyl-l, 2, 3, 6-tetrahydropyridine. Proc Natl Acad Set USA 80, 4546
Butterworth, R. F, Belanger, F, and Barbeau, A (1978) Hypokinesia produced by anterolateral hypothalamic 6-hydroxydopamine lesions and its reversal by some antiparkinson drugs Pharmacol Biochem Behav 8, 41–45
Collerton, D (1986) Cholinergic funtion and intellectual decline in Alzheimer’s disease Neuroscience 19, 1–28
Coyle, J. T, Price, D. L., and Delong, M R (1983) Alzheimer’s disease a disorder of cortical cholinergic innervation Science 219, 1184–1190
Crowther, R A (1995) Steps towards a mouse model of Alzheimer’s disease Bwessays 17, 593–595
Date, I and Ohmoto, T (1995) Neural transplantation and trophic factors in Parkinson’s disease special reference to chromaffin cell grafting, NGF support from pretransected peripheral nerve, and encapsulated dopamine-secreting cell grafting. Exp Neurol 137, 333–344.
Dietrich, W D (1994) Morphological manifestations of reperfusion injury in brain Ann NY Acad Set 723, 15–24
Dunnett, S B, and Svendsen, C N (1993) Huntington’s disease animal models and transplantation repair Cur Opin Neurbiol 3, 790–796
Duvoisin, R C and Marsden, C D. (1974) Reversal of reserpine-induced bradykinesia by a-methyldopa’ new light on its modus operandi Brain Res 71, 178–182
Dworsky, S and McCandless, D W (1987) Regional cerebral energy metabolism in bicucuhne-induced seizures Neurochem Res 12, 237–240
Emench, D W and Sanberg, P. R (1992) Animal models of Huntington’s disease, in Neuromethods vol 21 Animal Models of Neurological Disease, I, (Boulton, A A., Baker, G B., and Butterworth, R. F, eds), Humana, Clifton, NJ, pp 65–134
Flamm, E. S, Demopoulos, H B., Sehgman, M. L, Poser, R. G, and Ransohoff, J. (1978) Free radicals in cerebral ischemia Stroke 9, 445–447
Futrell, N, Watson, B D, Dietrich, W D., Prado, R., Milhkan, C, and Ginsberg, M. D (1988) A new model of embolic stroke produced by photochemical injury to the cartotid artery in the rat. Ann Neurol 23, 251–257
Games, D, Adams, D., Alessandnni, R., Barbour, R., Berthelette, P., Blackwell, C, Carr, Tv Clemens, J, Donaldson, T., and Gillespie, F (1995) Alzheimertype neuropathology in transgenic mice overpespressing V717F beta-amyloid precursor protein Nature 373, 523–527.
Ginsberg, M D and Busto, R. (1989) Rodent models of cerebral ischemia Stroke 20, 1627–1642
Goldstein, J M, Barnett, A, and Mahck, J B (1975) The evaluation of antiparkinson drugs on reserpine-induced rigidity m rats Eur Pharmacol 33, 183–188
Graham, D I., Bell, J. E, and Irnoside, J. W (1995) Color Atlas and Test of Neuropathology Mosby-Wolfe, London, pp 109, 113
Graham, D I and Lantos, P L, eds (1997) Greenfields’s Neuropathology, 6th ed Arnold, London, pp 329, 825
Hallmayer, D, Hossmann, K-A, and Mies, G (1985) Low dose of barbituates for prevention of hippocampal lesions after brief ischemic episodes Acta Neuropathol (Berl) 68, 27–31
Harrison, B M and McDonald, W I (1977) Remyehnation after transient experimental compression of the spinal cord Ann Neurol 1, 542–551
Hernandez, N E, Macdonall, J S, Stier, C T, Belmonte, A, Fernandez, R, and Karpiak, S E (1994) GM1 ganglioside treatment of spontaneously hypertensive stroke prone rats Exp Neurol 126, 95–100
Holtzman, D M, Li, Y W, Dearmond, S J, McKmley, M P, Gage, F H, Epstein, C J, and Mobley (1992) Mouse model of neurodegeneration atrophy of basal forebrain cholinergic neurons m trisomy 16 transplants Proc Nat Acad Sa USA 89, 11383–11387
Hornykiewicz, O and Kish, S J (1986) Biochemical pathophysiology of Parkinson’s disease. Adv Neurol 45, 19–34
Hyman, B T, Van Hoesen, G W, Damasio, A R, and Barnes, C L (1984) Alzheimer’s disease cell-specific pathology isolates the hippocampal formation Science 225, 1168–1170
Jarrard, L E, Kant, G J, Meyerhoff, J L, and Levy, A (1984) Behavioral and neurochemical effects of intraventricular AF64A administration in rats Pharmacol Bwchem Behav 21, 273–280
Johcoeur, F B, Rivest, R., and Drumheller, A (1991) Hypokinesia, rigidity and tremor induced by hypothalamic 6-OHDA lesions in the rat Brain Res Bull 26, 317–320
Kagstrom, E, Smith, M.-L, and Siesjo, B K (1983) Cerebral circulatory responses to hypercapnia and hypoxia in the recovery period following complete and incomplete cerebral ischemia in the rat Acta Physiol Scand 118, 281–291
Kahn, K (1972) The natural course of experimental cerebral infarction in the gerbil Neurology 22, 510–515
Kitagawa, K., Matsumoto, M, Handa, N, Fukunaga, R, Ueda, A., Isaka, Y, Kimura, K, and Kamada, T (1989) Prediction of stroke-prone gerbils and their cerebral circulation. Brain Res 479, 263–269
Kogure, K, Busto, R, Scheinberg, P, and Reinmuth, O M (1974) Energy metabolites and water content in rat brain during the early stage of development of cerebral infarction Brain 97, 103–114
Kohler, C and Schwarcz, R. (1983) Comparison of lbotenate and kainate neurotoxicity in rat brain a histological study Neuroscience 8, 819–835
Kornetsky, C (1977) Animal models promises and problems in Animal Models in Psychiatry and Neurology, (Hanin, I and Usdin, E, eds), Pergamon, Oxford, pp 18–29.
Kudo, M., Aoyama, A, Ichimon, S, and Fukanaga, N (1982) An animal model of cerebral infaction Homologous blood clot emboli in rats Stroke 13, 505–508
Lumsden, C E (1970) The neuropathology of multiple sclerosis, in Multiple sclerosis and Other Demyehnating Diseases Handbook of Clinical Neurology, (Vinken, P. J. and Bryun, G W., eds), North Holland Publishing, Amsterdam, pp. 217–209.
Lyden P D and Lonzo L (1994) Combination therapy protects ischemic brain in rats. A glutamate antagonist plus a gamma-aminobutyric acid antagonist Stroke 25, 189–196
Markowska, A L, Stone, W S, Ingram, D. K., Reynolds, J., Gold, P E, Conti, L H, Pontecorvo, M I, Wenk, G L., and Olton, D S (1989) Individual differences in aging-behavioral and neurobiological correlates Neurobiol Aging 10, 31–43
McCandless, D. W and Abel, M S (1992) Genetically based animal models of seizures, in Neuromethods vol 22, Animal models of Neurological Disease, II, (Boulton, A A, Baker, G B, and Butterworth, R F., eds), Humana, Clifton, NJ, pp 169–182
McGeer, P L and McGeer, E G (1982) Kainic acid’ the neurotoxic breakthrough CRC Cut Rev Toxicol 10, 1–26
Mori, N. and Wada, J A. (1987) Bidirectinal transfer between kindling induced by excitatory amino acids and electrical stimulation Brain Res 425, 45–48
Nowak, T S (1985) Synthesis of a stress protein following transient ischemia in the gerbil J Neurochem 45, 1635–1641
O’Brien, M D and Waltz, A G (1973) Transorbital approach for occluding the middle cerebral artery without craniotomy Stroke 4, 201–206
Olfert, E D (1992) Ethics of animal models of neurological diseases, in Neuromethods, vol 21, Animal Models of Neurological Disease, I, (Boulton, A A, Baker, G B, and Butterworth, R F, eds), Humana, Clifton, NJ, pp 1–28
Pendlebury, W W., Beal, M F, Kowall, N W, and Soloman, P R (1988) Neuropathology, neurochemical and immunocytochemical characertisitics of aluminum-induced neurofilamentous degeneration Neurotoxicology 9, 503–510
Poirier, L J. (1960) Experimental and histological study of midbrain dyskinesias J Neurophyswl 23, 534–551-
Poirier, L. J and Sourkes, T L (1965) Influence of the substantia nigra on the catecholamine content of the striatum Brain 88, 181–182
Pontecorvo, M J, Wenk, G L, and Olton, D S (1989) Individual differences in aging behavioral and neurobiolgical correlates Neurobiol Aging 10, 31–43
Post, R M, Kennedy, C, Shinohara, M, Squillace, K., Miyaoko, M, Suda, S, Inguar, D H, and Sokoloff, L (1984) Metabolic and behavioral consequences of lidocaine-kindled seizures. Brain Res. 324, 295–303.
Post, R. M., Weiss, S R B, and Pert, A (1988) Cocaine-induced behavioral sensitization and kindling implications for the emergence of psychopathology and seizures Ann NY Acad Set. 537, 292–308
Preston, G C, Brazell, C, Ward, C, Boks, P., Traub, M., and StahL S. M. (1989) The scopolamine model of dementia determination of central chohnomimentic effects of physostigmme on cognition and biochmical marker in man. J Psychopharmacol 2, 67–79
Price, D. L (1986) New perspectives on Alzheimer’s disease Ann Rev Neurosci 9, 489–512
Private, A, Jacque, C, and Bourre, J M (1979) Absence of the major dense line m myelin of the nutant mouse’ shiverer’ Neurosci Lett 12, 107–112
Przedborski, S, Levivier, M, Jiang, H, Ferreira, M, Jackson-Lewis, V, Donaldson, D, and Togasaki, D M (1995) Dose-dependent lesions of the dopaminergic nigrostnatal pathway induced by intrastnatal injection of 6-hydroxydopamine Neurosaence 67, 631–647
Rapp, P R, Rosenberg, R. A., and Gallagher, M (1987) An evaluation of spatial information processing in aged rats Behav Neurosci 101, 3–12
Roach, A, Boylan, K and Horvath, S (1983) Characterization of cloned DNA representing rat myelin basic protein absence of expression in Shiverer mutant mice Cell 34, 799–806
Rondeau, D B, Johcoeur, F B, Belanger, F, and Barbeau, A (1978) Differential behavioral activities from anterior and posterior hypothalamic lesions in the rat. Pharmacol Bwchem Behav 9, 43–47
Rosenbluth, J (1980) Central myelin in the mouse mutant shiverer J Comp Neurol 194, 639–648
Sanberg, P R, Koutouzis, T K, Freeman, T B, Cahill, D W, and Norman, A B (1993) Behavioral effects of fetal neural transplants relevance to Huntington’s disease Brain Res Bull 32, 493–496
Scaravilh, F (1985) Twitcher a neurological mutant mouse with globoid-cell leukodystrophy, in The Pathology of the Myelinated Axon, (Masazumi, A, Hirano, A and Aronson, S M, eds), Igaku-Shoin, New York, pp 150–176
Schulz, J B and Beal, M F (1994) Mitochondrial dysfunction in movement disorders Curr Opin Neurol 7, 333–339
Selman, W R, Ricci, A J, Crumnne, R C, LaManna, J C, Ratcheson, R A, and Lust, W D (1990) The evolution of focal ischemic damage a metabolic analysis Metab Brain Dis 5, 33–44
Seta, K A, Crumnne, C R, Whittingham, T S, Lust, W D, and McCandless, D W (1992) Experimental models of human stroke, in Neuromethods vol 22 Animal Models of Neurological Disease, II (Boulton, A A, Baker, G B, and Butterworth, R F, eds) Humana, Clifton, NJ, pp 1–50
Shigeno, T, Teasdale, G M, McCulloch, J, and Graham, D I. (1985) Recirculation model following MCA occlusion in rats J Neurosurg 63, 272–277
Sidman, R. L, Dickie, M. M., and Appel, S. H (1964) Mutant mice (Quaking and Jimpy) with deficient myehnation in the central nervous system Science 144, 309–311
Smith, M-L., Auer, R N, and Siesjo, B K (1984) The density and distribution of ischemic brain injury in the rat following 20-10 mm of forebrain ischemia Acta Neuropathol (Berl) 64, 319–332
Smith, G P, Strohmayer, A J, and Reis, D J (1972) Effect of lateral hypothalamic injections of 6-hydroxydopamine on food and water intake in rats Nature 235, 27–29
Troncoso, J C, Price, D L, Griffin, J W, and Parhad, I M (1982) Neurofibrillary axonal pathology in aluminum intoxication Ann Neurol 12, 278–283
Ungerstedt, U, Avemo, A, Avemo, E, Ljungber, T, and Range, C (1973) Animal models of parkinsonism Adv Bwchem Psychopharmacol 9, 707–715
Vonsattel, J-P, Myers, R H, and Stevens, T J (1985) Neuropathological classification of Huntington’s disease J Neuropathol Exp Neurol 44, 559–577
Von Voightlander, P F and Moore, K E (1973) Turning behavior in mice with unilateral 6-hydroxydopamine lesions in the striatum effects of apomorphine L-DOPA, amantadine, amphetamine and other psychomotor stimulants Neuropharmacology 12, 451–462
Welch, F. A., Sakamoto, T, McKee, A E, and Sims, R (1987) Effect of lactacidosis on pyridine nucleotide stability during ischemia in the mouse brain J Neurochem 49, 846–851
Wenk, G L (1992) Animal models of Alzheimer’s disease, in Neuromethods vol 21 Animal Models of Neurological Disease, I (Boulton, A A, Baker, G B, and Butterworth, R F. eds.) Humana, Clifton, NJ, pp. 29–63
Wiederholt, W C (1995) Neurology for Non-Neurologists, 3rd ed Saunders, Philadephia
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Todd, K.G., Butterworth, R.F. (1998). Animal Models of Neurological Disorders. In: In Vivo Neuromethods. Neuromethods, vol 32. Humana Press. https://doi.org/10.1385/0-89603-511-5:149
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